Table 3.

Mitochondria targeted biosimilar or bioengineered medicines other than ALS indications.

S. No.	Interventions	Mechanism	Disease Condition	References
1	Mitochondrial Replacement Therapy (MRT)	Restraint of mutated mitochondrial DNA transfer through mitochondrial donation procedures like maternal spindle transfer and pronuclear transfer in the oocyte or fertilized embryo is replaced with healthy copies of the mitochondrial genome	Mitochondrial dysfunction	[119, 167]
2	dNTPs therapy	Interruption of deoxyribonucleotide metabolism, which contributes to restricted availability of various deoxyribonucleoside triphosphates (dNTPs)	Mitochondrial DNA depletion syndrome (MDS) and Mitochondrial neuroastrointestinal encephalomyopathy (MNGIE)	[119, 168, 169]
3	Stem cell replacement/ transplantation therapies	Allogeneic Hematopoietic Stem Cell Transplant (HSCT)	Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)	[170, 171]
4	Gene therapy	Gene replacement therapy: Leber’s hereditary optic neuropathy (LHON), caused by mutations in the mitochondrially-encoded MT-ND4 gene	Leber’s hereditary optic neuropathy (LHON) is due to missense point mutations affecting mitochondrial DNA (mtDNA), usually found in the homoplasmic state, leading to mitochondrial dysfunction.	[172, 173]
5	Correction of DNA Heteroplasmy	Manipulating or selective elimination of mitochondrial DNA heteroplasmy by a mitochondrially targeted restriction endonuclease	Neuropathy, ataxia & retinitis pigmentosa (NARP), MILS syndromes	[174-176]
6	tRNAs synthase correction	Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation.	Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes	[177]
7	Elamipretide (MTP-131), a novel mitochondria-targeting tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2)	Stabilizes cardiolipin and enhances ATP synthesis in multiple organs, including the heart, kidney, neurons, and skeletal muscle	Impaired mitochondrial energy metabolism	[178]